Summary Background Pili annulati is an autosomal dominant hair shaft disorder characterized by alternating light and dark bands in hairs of affected individuals. Recently, a locus for pili annulati was mapped to chromosome 12q24.32-24.33 and recombination events defined a critical region of 9.2 cM (3.9 Mb). Objectives The aim of the current study was to narrow the size of the candidate region and to identify the pathogenic mutation for pili annulati by analysing the candidate genes. Methods In three families with 90 individuals, including 40 affected subjects, linkage analysis was performed with 13 microsatellite markers in the candidate region on chromosome 12. Candidate genes were analysed for their expression in hair follicles and other tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) and mutation analysis. Results Multipoint LOD score analysis for all three families confirmed the locus on the long arm of chromosome 12 with a maximum LOD score of 12.26 at marker D12S357. In two families, recombinations were identified which narrowed the region to 2.9 Mb containing 36 genes. We analysed the candidate genes in this region by RT-PCR and found that 24 were expressed in human hair follicles. Based on the result of the expression analysis, DNA sequencing of the coding region of the candidate genes was performed; this did not result in the discovery of a causal mutation. Conclusion We reduced the critical interval of pili annulati to 2.9 Mb and excluded mutations in the coding region of all 36 possible candidate genes by sequence analysis.

Pili annulati: refinement of the locus on chromosome 12q24.33 to a 2.9-Mb interval and candidate gene analysis

TOSTI, ANTONELLA;
2009

Abstract

Summary Background Pili annulati is an autosomal dominant hair shaft disorder characterized by alternating light and dark bands in hairs of affected individuals. Recently, a locus for pili annulati was mapped to chromosome 12q24.32-24.33 and recombination events defined a critical region of 9.2 cM (3.9 Mb). Objectives The aim of the current study was to narrow the size of the candidate region and to identify the pathogenic mutation for pili annulati by analysing the candidate genes. Methods In three families with 90 individuals, including 40 affected subjects, linkage analysis was performed with 13 microsatellite markers in the candidate region on chromosome 12. Candidate genes were analysed for their expression in hair follicles and other tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) and mutation analysis. Results Multipoint LOD score analysis for all three families confirmed the locus on the long arm of chromosome 12 with a maximum LOD score of 12.26 at marker D12S357. In two families, recombinations were identified which narrowed the region to 2.9 Mb containing 36 genes. We analysed the candidate genes in this region by RT-PCR and found that 24 were expressed in human hair follicles. Based on the result of the expression analysis, DNA sequencing of the coding region of the candidate genes was performed; this did not result in the discovery of a causal mutation. Conclusion We reduced the critical interval of pili annulati to 2.9 Mb and excluded mutations in the coding region of all 36 possible candidate genes by sequence analysis.
2009
Giehl KA; Rogers MA; Radivojkov M; Tosti A; de Berker DA; Weinlich G; Schmuth M; Ruzicka T; Eckstein GN.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/71502
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